This study concerns the enhancement of the antineoplastic effects of FUdR by benzyloxybenzylacyclouridine (BBAU), a potent uridine phosphorylase inhibitor. Using the human pancreatic carcinoma (DAN) cell line, preliminary results have been obtained. In culture, FUdR (10 to the minus 7 M) produced low inhibition. However, pretreatment with a noninhibitory level of BBAU increased FUdR inhibition to greater than 100%. In the ATS mouse xenograft model, low dosage BBAU significantly increased the antitumor activity of FUdR from 10 to 80%. Similar investigations will be carried out with two human breast carcinoma and two colorectal carcinoma cell lines (HCT-8, HRT-18). In correlation with BBAU-FUdR sensitivities, the uridine and thymidine phosphorylase levels of these cell lines will be measured. Studies with 3H-FUdR and 3H-UdR will determine the effects fo BBAU on the incorporation of FUdR and UdR respectively, into cold acid-soluble, RNA and DNA fractions. This will shed new light on the biochemical events leading to cell death. The proposed research effort should ultimately result in an improved clinical fluoropyrimidine chemotherapy.